Frontiers in heart failure: sodium, longitudinal strain, contractility sensor, fatal arrhythmias, and stroke

This Focus Issue on Heart Failure begins with the Current Opinion contribution ‘The year in cardiology 2016: heart failure’, authored by Aldo P. Maggioni and colleagues from the ANMCO Research Center in Florence, Italy.1 The current year has been mainly characterized by the publication both in Europe2 and in the USA of Guidelines3 for the diagnosis and treatment of heart failure, with the praiseworthy effort to provide consistent recommendations. Therefore, the large majority of new evidence published at the end of 2015 and in the first quarter of 2016 is included in these publications. However, as always happens, the scientific community has been provided, more recently, with additional information from new studies very relevant for the management of patients with heart failure. Sodium intake is an important, yet controversial issue in hypertension and heart failure.4 While US professional societies, in particular, recommend a strict sodium diet in many of these patients,5 others are less strict and consider a U-shape relationship between sodium and cardiovascular events.6 Indeed, harm caused by even a very low sodium diet has been reported, particularly in heart failure.7 In a ‘WHF Position Statement on sodium intake’, Jagat Narula and colleagues from the Mount Sinai St. Luke’s and Mount Sinai West in New York reiterate that defining an optimal range of sodium intake in populations has been challenging and controversial.8 Clinical trials evaluating the effect of sodium reduction on blood pressure have shown blood pressure-lowering effects due to sodium intake of <1.5 g/day. Findings from these blood pressure trials form the basis for current guideline recommendations to reduce sodium intake to <2.3 g/day. However, these clinical trials employed interventions that are not feasible for population-wide implementation (i.e. feeding studies or intensive behavioural interventions), particularly in low- and middle-income countries. Prospective cohort studies have identified the optimal range of sodium intake to reside in the moderate range (3–5 g/day), where the risk of cardiovascular disease and death is lowest. Therefore, there is consistent evidence from clinical trials and observational studies to support reducing sodium intake to <5 g/day in populations, but inconsistent evidence for further reductions below a moderate intake range (3–5 g/day). Unfortunately, there are no large randomized controlled trials comparing low sodium intake, equivalent to < 3 g/day, with moderate sodium intake, i.e. 3–5 g/day, in general populations to determine the net clinical effects of low sodium intake. Until such trials are completed, it is likely that controversy regarding the optimal sodium intake range will continue. This working group calls for the completion of large definitive clinical trials to clarify the range of sodium intake for optimal cardiovascular health within the moderate to low intake range. The authors support interventions to reduce sodium intake in populations who consume high sodium intake, i.e. >5 g/day, which should be embedded in an overall healthy dietary pattern. Pump function of the left ventricle is usually assessed by ejection fraction. In the presence of valvular heart disease, particularly mitral regurgitation, this parameter may overestimate the contractile status of the left heart.9 Left ventricular global longitudinal strain reflects left ventricular systolic function more precisely and correlates inversely with the extent of left ventricular myocardial scar and fibrosis.10 In an ESC Fast Track Clinical Trial Update ‘Prognostic implications of left ventricular global longitudinal strain in heart failure patients with narrow QRS complex treated with cardiac resynchronization therapy: a subanalysis of the randomized EchoCRT trial’, Jeroen J. Bax and colleagues from the Leiden University Medical Center investigated the prognostic value of left ventricular global longitudinal strain in patients with narrow QRS complex.11 Left ventricular global longitudinal strain was measured on the apical two-, four-, and three-chamber views using speckle tracking analysis. Measurement of baseline left ventricular global longitudinal strain was feasible in 755 patients. The median value of left ventricular global longitudinal strain in the overall population was 7.9%. After 19 months, 95 patients without cardiac resynchronization therapy, i.e. the CRT-OFF group, and 111 in the CRT-ON group reached the combined primary endpoint of all-cause mortality and heart failure hospitalization. Each 1% absolute unit decrease in left ventricular global longitudinal strain was independently associated with an 11% increase in the risk of reaching the primary endpoint after adjusting for ischaemic cardiomyopathy and randomization treatment among other clinically relevant variables. When categorizing patients according to quartiles of left ventricular global longitudinal strain, the primary endpoint occurred more frequently in patients in the lowest quartile, i.e. <6.2%, specifically in 46% treated with CRT-ON and in 29% with CRT-OFF, whereas no differences were observed in patients with left ventricular global longitudinal strain ≥6.2% treated with CRT-OFF or CRT-ON. The authors conclude that low left ventricular global longitudinal strain is associated with poor outcome in heart failure patients with QRS width <130 ms, independent of randomization to cardiac resynchronization therapy or not. Importantly, in the group of patients with the lowest left ventricular global longitudinal strain quartile, cardiac resynchronization therapy may have a detrimental effect on clinical outcomes. The manuscript is accompanied by an Editorial authored by Ole Alexander Breithardt from the AGAPLESION Diakonie Kliniken Kassel in Kassel, Germany.12 Although cardiac resynchronization therapy is effective in patients with systolic heart failure and a wide QRS interval,13 a substantial proportion of patients remain non-responsive.14 The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular and interventricular timings. In a clinical research manuscript entitled ‘Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial’, Josep Brugada and the RESPOND CRT Investigators noted that the RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in heart failure patients undergoing cardiac resynchronization therapy.15 Freedom fromall-cause mortality or heart failure hospitalization. CI, confidence interval; HR, hazard ratio. (from Brugada J, Delnoy PP, Brachmann J, Reynolds D, Padeletti L, Noelker G, Kantipudi C, Rubin Lopez JM, Dichtl W, Borri-Brunetto A, Verhees L, Ritter P, Singh JP, RESPOND CRT Investigators. Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial. See pages 730–738.) Comparison of observed and expected stroke rates after 3 years for patients categorized by tertile of risk-score derived from the heart failure with reduced ejection fraction stroke model. Observed shows the 3 year Kaplan–Meier rate for each tertile; expected shows estimate from the Cox model for each tertile. (from Abdul-Rahim AH, Perez A-C, MacIsaac RL, Jhund PS, Claggett PL, Carson PE, Komajda M, McKelvie RS, Zile MR, Swedberg K, Yusuf S, Pfeffer MA, Solomon SD, Lip GYH, Lees KR, and McMurray JJV, on behalf of the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity-Preserved (CHARM-Preserved) and the Irbesartan in Heart Failure with Preserved Systolic Function (I-Preserve) Steering Committees. Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials. See pages 742–750.) Heart failure has been subdivided into those with reduced (heart failure with reduced ejection fraction or HFrEF) and those with preserved pump function (heart failure with preserved ejection fraction or HFpEF). Recently, the new ESC Guidelines have introduced a third group, i.e. those with a midrange ejection fraction or HFmrEF.2 All forms of heart failure are associated with an array of complications, from decompensation leading to repeated hospitalizations17 to arrhythmias, mitral regurgitation,18 and fatal pump failure. In those developing atrial fibrillation, stroke is an additional major cardiovascular event. On the other hand, the incidence and predictors of stroke in patients with HFpEF,19 but without atrial fibrillation, are unknown. This issue has been addressed by John J.J.V. McMurray and colleagues from the Western Infirmary in Glasgow, UK in their research article entitled ‘Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve Trials’.20 To that end they pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, they derived a model for stroke in such patients and compared its performance with a published model in patients with HFrEF. The two stroke models were compared and Kaplan–Meier curves for stroke estimated. The risk model was validated in a third HFpEF trial. Of the 6701 patients, 4676 did not have atrial fibrillation. Stroke occurred in 6.1% of those with atrial fibrillation and in 3.7% in those without it. There was no difference in performance of the stroke model derived in the HFpEF cohort and the published HFrEF model as the predictive variables overlapped (Figure 2). The model performed well in the validation cohort. The rate of stroke in patients in the upper third of risk approximated to that in patients with atrial fibrillation. McMurray et al. conclude that a small number of clinical variables, specifically age, body mass index, NYHA class, history of stroke, and insulin-treated diabetes, identify a subset of patients with HFpEF, but without atrial fibrillation, at elevated risk of stroke. In a final research article entitled ‘Incidence and predictors of sudden death, major conduction defects, and sustained ventricular tachyarrhythmias in 1388 patients with myotonic dystrophy type 1’, Karim Wahbi and colleagues from the Cochin Hospital in Paris, France describe the incidence and predictors of sudden death, major conduction defects, and sustained ventricular tachyarrhythmias in myotonic dystrophy type 1.21 They retrospectively enrolled 1388 adults with myotonic dystrophy type 1 referred to six French medical centres, confirmed their vital status, classified all deaths, and determined the incidence of major conduction defects requiring permanent pacing and sustained ventricular tachyarrhythmias. Over a median 10-year follow-up, 18% of the patients died, 3.6% suddenly. Analysis of the cardiac rhythm at the time of the 39 sudden deaths revealed sustained ventricular tachyarrhythmias in nine, asystole in five, complete atrioventricular block in one, and electromechanical dissociation in two patients. Non-cardiac causes were identified in the five patients with sudden death who underwent autopsies. Major conduction defects developed in 19% and sustained ventricular tachyarrhythmias in 2% of patients. By Cox regression analysis, age, family history of sudden death, and left bundle branch block were independent predictors of sudden death, while age, male sex, ECG conduction abnormalities, syncope, and atrial fibrillation were independent predictors of major conduction defects. Non-sustained ventricular tachyarrhythmias was the only predictor of sustained ventricular tachyarrhythmias. The authors conclude that sudden death is a frequent mode of death in myotonic dystrophy type 1, with multiple mechanisms involved. Major conduction defects were by far more frequent than sustained ventricular tachyarrhythmias, whose only independent predictor was a personal history of non-sustained ventricular tachyarrhythmias. The editors hope that readers of this issue of the European Heart Journal will find it of interest to them.